The cycad genotoxin methylazoxymethanol, linked to Guam ALS/PDC, induces transcriptional mutagenesis

Verheijen, Bert M.; Chung, Claire; Thompson, Ben; Kim, Hyunjin; Nakahara, Asa; Anink, Jasper J.; Mills, James D.; ,; Phatnani, Hemali; Kwan, Justin; Sareen, Dhruv; Broach, James R.; Simmons, Zachary; Arcila-Londono, Ximena; Lee, Edward B.; Van Deerlin, Vivianna M.; Shneider, Neil A.; Fraenkel, Ernest; Ostrow, Lyle W.; Baas, Frank; Zaitlen, Noah; Berry, James D.; Malaspina, Andrea; Fratta, Pietro; Cox, Gregory A.; Thompson, Leslie M.; Finkbeiner, Steve; Dardiotis, Efthimios; Miller, Timothy M.; Chandran, Siddharthan; Pal, Suvankar; Hornstein, Eran; MacGowan, Daniel J.; Heiman-Patterson, Terry; Hammell, Molly G.; Patsopoulos, Nikolaos A.; Butovsky, Oleg; Dubnau, Joshua; Nath, Avindra; Bowser, Robert; Harms, Matthew; Aronica, Eleonora; Poss, Mary; Phillips-Cremins, Jennifer; Crary, John; Atassi, Nazem; Lange, Dale J.; Adams, Darius J.; Stefanis, Leonidas; Gotkine, Marc; Baloh, Robert H.; Babu, Suma; Raj, Towfique; Paganoni, Sabrina; Shalem, Ophir; Smith, Colin; Zhang, Bin; Harris, Brent; University of Maryland Brain and Ti,; Broce, Iris; Drory, Vivian; Ravits, John; McMillan, Corey; Menon, Vilas; Wu, Lani; Altschuler, Steven; Lerner, Yossef; Sattler, Rita; Van Keuren-Jensen, Kendall; Rozenblatt-Rosen, Orit; Lindblad-Toh, Kerstin; Nicholson, Katharine; Gregersen, Peter; Lee, Jeong-Ho; Maze Therapeutics,; Bristol-Myers Squibb,; Koks, Sulev; Muljo, Stephen; Traynor, Bryan J.; Pfizer,; Regeneron,; Insitro,; Lee, Jeong H.; Aronica, Eleonora; Oyanagi, Kiyomitsu; Kakita, Akiyoshi; Gout, Jean-Francois; Vermulst, Marc

doi:10.1186/s40478-024-01725-y

Cited by 5 publications

(1 citation statement)

References 22 publications

(28 reference statements)

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“…The concentration of residual cycasin in seed flour was strongly correlated with the very high incidence of ALS among the native people of Guam (Chamorros) and immigrants who adopted a Chamorro lifestyle [ 11 , 20 , 26 ]. MAM is a genotoxin that induces DNA damage and transcriptional mutagenesis in murine brain cells [ 12 , 27 ] and modulates brain cellular pathways involved in neurodegenerative disease [ 24 ]. Notably, the latent period between exposure to cycasin and the clinical appearance of ALS spanned years or decades, comparable to the latency periods between consumption of false morels and diagnosis of ALS in the present French cases.…”

Section: Discussionmentioning

confidence: 99%

Corrected speciation and gyromitrin content of false morels linked to ALS patients with mostly slow-acetylator phenotypes

Lagrange,

Loriot,

Chaudhary

et al. 2024

eNeurologicalSci

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Section: Discussionmentioning

confidence: 99%

Corrected speciation and gyromitrin content of false morels linked to ALS patients with mostly slow-acetylator phenotypes

Lagrange,

Loriot,

Chaudhary

et al. 2024

eNeurologicalSci

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Effects of the glyphosate-based herbicide roundup on C. elegans and S. cerevisiae mortality, reproduction, and transcription fidelity

Dinep-Schneider,

Appiah,

Dapper

et al. 2024

Environmental Pollution

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Transcript errors generate amyloid-like proteins in human cells

Chung,

Kou,

Shemtov

et al. 2024

Nat Commun

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Aging is characterized by the accumulation of proteins that display amyloid-like behavior. However, the molecular mechanisms by which these proteins arise remain unclear. Here, we demonstrate that amyloid-like proteins are produced in a variety of human cell types, including stem cells, brain organoids and fully differentiated neurons by mistakes that occur in messenger RNA molecules. Some of these mistakes generate mutant proteins already known to cause disease, while others generate proteins that have not been observed before. Moreover, we show that these mistakes increase when cells are exposed to DNA damage, a major hallmark of human aging. When taken together, these experiments suggest a mechanistic link between the normal aging process and age-related diseases.

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The cycad genotoxin methylazoxymethanol, linked to Guam ALS/PDC, induces transcriptional mutagenesis

Cited by 5 publications

References 22 publications

Corrected speciation and gyromitrin content of false morels linked to ALS patients with mostly slow-acetylator phenotypes

Corrected speciation and gyromitrin content of false morels linked to ALS patients with mostly slow-acetylator phenotypes

Effects of the glyphosate-based herbicide roundup on C. elegans and S. cerevisiae mortality, reproduction, and transcription fidelity

Transcript errors generate amyloid-like proteins in human cells

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